Structure of PAMAM Dendrimers:  Generations 1 through 11

Abstract

The structure and dynamics of poly(amido amide) (PAMAM) dendrimers have been of great interest both scientifically and industrially, but such important features as the distributions of atoms, channels, and strain inside these molecules remain unresolved. This paper reports results from systematic investigations of the atomistic structure of ethylenediamine (EDA) cored PAMAM dendrimer up through the 11th generation (294 852 atoms), at which point the strain energy has risen to a point that limits uniform growth of additional layers. Here we report, as a function of generation, structural properties such as radius of gyration, shape tensor, asphericity, fractal dimension, monomer density distribution, solvent accessible surface area, molecular volume, and end group distribution functions, all evaluated from extensive molecular dynamics (MD) at 300 K. We find that the radius of gyration scales as R g ∼ N 1/3 over the entire range of generations, suggesting rather uniform space filling for all generations. Contrary to common expectation, we find that the outer subgenerations penetrate substantially into the interior of the dendrimer, even for G11. Consequently, the terminal amine groups are distributed throughout the interior, not just on the periphery of the dendrimer. However for G6 through G11 there is a large region of uniform density, supporting the uniform scattering model often used in interpreting the SANS (small-angle neutron scattering) and SAXS (small-angle X-ray scattering) data, which lead to sizes in excellent agreement with the calculations. The calculated single particle form factor approaches that of a sphere as the generation number increases. For the larger generations, we found that the use of continuous configuration biased Monte Carlo (CCBB MC) was essential to construct initial configurations that lead to lower final strain energies.

Epidermal Growth Factor–PEG Functionalized PAMAM-Pentaethylenehexamine Dendron for Targeted Gene Delivery Produced by Click Chemistry

“…This was most likely attributed to the condensed topological structure of PAMAM dendrons with longer oligoamine terminal chains. 47 The molecular weight polydispersity (PDI) of DETA-, TETA-, TEPA-, or PEHAmodified PAMAM dendron became broader compared to that of PAMAM-EDA or PAMAM-DEA dendron, indicating the occurrence of intermolecular cross-linking during the amidation process. The termini secondary amino densities were calculated according to the 1 H NMR spectra determined substitution degrees.…”

Association of a Weakly Acidic Anti-Inflammatory Drug (Ibuprofen) with a Poly(Amidoamine) Dendrimer as Studied by Molecular Dynamics Simulations

“…Atomistic molecular models of the G3 PAMAM dendrimer were obtained from an earlier work. 33 At the initial stage of the construction of the dendrimer/drug models, ibuprofen molecules were placed within a spherical shell of width comparable to the dendrimer's radius of gyration around the dendrimer periphery (i.e., the maximum distance from the dendrimer's center of mass was twice the radius of gyration of the dendrimer). As noted earlier, to maintain charge neutrality, addition of an appropriate number of Cl -counterions in neutral and low pH conditions was made, whereas in the case of ionized ibuprofen, Na + counterions were included instead.…”

Structure and Dynamics of DNA−Dendrimer Complexation: Role of Counterions, Water, and Base Pair Sequence

“…The initial structure of G2-G4 PAMAM dendrimers at various protonation levels was taken from our previous study 22,25 . At intermediate or neutral pH (pH ~ 7) all the primary amines (16 for G2, 32 for G3 and 64 for G4) are protonated.…”